Senior Vice Chancellor's Research Seminar

Topic Overview:

Cancer is a genetic disease caused by somatic or germline alterations of the genome. In the last decade, enormous efforts have been made to better characterize the cancer genome and identify novel therapies. Those efforts led to many insightful discoveries but also raised a challenge: In some cancer types (e.g., melanoma and thyroid cancer), a subgroup of patients have very few somatic and germline alterations in protein-coding genes. Mechanisms of these tumors’ initiation and progression remain mysterious.

Accumulating evidence has indicated that non-protein-coding components (ncRNAs) of the genome, such as long noncoding RNA (lncRNA) and microRNA (miRNA) genes, can act as tumor suppressors and oncogenes, therefore helping to explain the genomics “dark matter” in cancer. However, in contrast to the exciting insights into downstream regulatory functions of miRNA and lncRNA, the upstream scenarios of ncRNA dysregulation (i.e., copy number and DNA methylation alteration) in tumors remains unclear. The lack of information about ncRNA genetic and epigenetic alterations in tumors has largely hindered the exploration of ncRNAs’ role in cancer.

Taking advantage of a wealth of genome-wide cancer sequence data, the Yang lab developed a set of computational methods and analytic strategies to characterize the genetic and epigenetic landscape of ncRNA genes. This landscape includes genome-wide alterations in copy number, DNA methylation, and transcriptomes of more than 10,000 noncoding genes in more than 3,000 tumor cases with known clinical features. In addition to the global genetic and epigenetic landscape of ncRNA genes in cancer, Yang will discuss several case studies using in vitro and in vivo functional assays, which successfully demonstrated that epigenetic silencing of ncRNA is an essential molecular event leading to cancer progression and drug resistance. The future direction for the Yang lab will be developing novel approaches to sensitively detect cancer-related noncoding genes and combining integrated genomic and functional studies to identify the underlying mechanisms of ncRNAs in cancer progression and drug resistance.









		Topic Overview: Cancer is a genetic disease caused by somatic or germline alterations of the genome. In the last decade, enormous efforts have been made to better characterize the cancer genome and identify novel therapies. Those efforts led to many insightful discoveries but also raised a challenge: In some cancer types (e.g., melanoma and thyroid cancer), a subgroup of patients have very few somatic and germline alterations in protein-coding genes. Mechanisms of these tumors’ initiation and progression remain mysterious. Accumulating evidence has indicated that non-protein-coding components (ncRNAs) of the genome, such as long noncoding RNA (lncRNA) and microRNA (miRNA) genes, can act as tumor suppressors and oncogenes, therefore helping to explain the genomics “dark matter” in cancer. However, in contrast to the exciting insights into downstream regulatory functions of miRNA and lncRNA, the upstream scenarios of ncRNA dysregulation (i.e., copy number and DNA methylation alteration) in tumors remains unclear. The lack of information about ncRNA genetic and epigenetic alterations in tumors has largely hindered the exploration of ncRNAs’ role in cancer. Taking advantage of a wealth of genome-wide cancer sequence data, the Yang lab developed a set of computational methods and analytic strategies to characterize the genetic and epigenetic landscape of ncRNA genes. This landscape includes genome-wide alterations in copy number, DNA methylation, and transcriptomes of more than 10,000 noncoding genes in more than 3,000 tumor cases with known clinical features. In addition to the global genetic and epigenetic landscape of ncRNA genes in cancer, Yang will discuss several case studies using in vitro and in vivo functional assays, which successfully demonstrated that epigenetic silencing of ncRNA is an essential molecular event leading to cancer progression and drug resistance. The future direction for the Yang lab will be developing novel approaches to sensitively detect cancer-related noncoding genes and combining integrated genomic and functional studies to identify the underlying mechanisms of ncRNAs in cancer progression and drug resistance.